Bacteroides forsythus has emerged as a crucial periodontal pathogen with possible implications for systemic disease. The aim of this study was to isolate the S-layer from B. forsythus and examine its virulence potential as a part of efforts to characterize virulence factors of B. forsythus. The role of the S-layer in the haemagglutinating and adherent/invasive activities was evaluated. It was observed that the S-layer alone was able to mediate haemagglutination. In adherent and invasive studies, transmission electron microscopy clearly revealed that B. forsythus cells were able to attach to and invade KB cells, showing the formation of a microvillus-like extension around adherent and intracellular bacteria. The quantitative analysis showed that five different B. forsythus strains exhibited attachment (1.9-2.3 %) and invasion (0.4-0.7 %) capabilities. It was also observed through antibody inhibition assays that adherent/invasive activities of B. forsythus are mediated by the S-layer. Furthermore, an in vivo immunization study adopting a murine abscess model was used to prove that the S-layer is involved in the infectious process of abscess formation. While mice immunized with purified S-layer and B. forsythus whole cells did not develop any abscesses when challenged with viable B. forsythus cells, unimmunized mice developed abscesses. Collectively, the data obtained from these studies indicate that the S-layer of B. forsythus is a virulence factor.